Cefpodoxime Proxetil

Cefpodoxime proxetil is indicated for the treatment of patients with mild to moderate infections caused by susceptible strains of the designated microorganisms in the conditions listed below. 

caused by (excluding penicillin-resistant strains), , (including beta-lactamase-producing strains), or (including beta-lactamase-producing strains). 



caused by .



Only penicillin by the intramuscular route of administration has been shown to be effective in the prophylaxis of rheumatic fever. Cefpodoxime proxetil is generally effective in the eradication of  streptococci from the oropharynx. However, data establishing the efficacy of cefpodoxime proxetil for the prophylaxis of subsequent rheumatic fever are not available.



caused by or(including beta-lactamase-producing strains). 



caused by , (non-beta-lactamase-producing strains only), or . Data are insufficient at this time to establish efficacy in patients with acute bacterial exacerbations of chronic bronchitis caused by beta-lactamase-producing strains of . 



caused by (including penicillinase-producing strains). 



due to (including penicillinase-producing strains). 



The efficacy of cefpodoxime in treating male patients with rectal infections caused by has not been established. Data do not support the use of cefpodoxime proxetil in the treatment of pharyngeal infections due to in men or women. 



caused by (including penicillinase-producing strains) or . Abscesses should be surgically drained as clinically indicated. 



In clinical trials, successful treatment of uncomplicated skin and skin structure infections was dose-related. The effective therapeutic dose for skin infections was higher than those used in other recommended indications. (See .) 



caused by (including beta-lactamase-producing strains), , and . 



caused by , or . 



In considering the use of cefpodoxime proxetil in the treatment of cystitis, cefpodoxime proxetil’s lower bacterial eradication rates should be weighed against the increased eradication rates and different safety profiles of some other classes of approved agents. (See section.) 



Appropriate specimens for bacteriological examination should be obtained in order to isolate and identify causative organisms and to determine their susceptibility to cefpodoxime. Therapy may be instituted while awaiting the results of these studies. Once these results become available, antimicrobial therapy should be adjusted accordingly. 



To reduce the development of drug-resistant bacteria and maintain the effectiveness of cefpodoxime proxetil and other antibacterial drugs, cefpodoxime proxetil should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Cefpodoxime proxetil tablets should be administered orally with food to enhance absorption. (See .)



The recommended dosages, durations of treatment, and applicable patient population are as described in the following chart: 

Adults and Adolescents (age 12 years and older):

Type of Infection	Total Daily Dose	Dose Frequency	Duration
Pharyngitis and/or tonsillitis	200 mg	100 mg Q 12 hours	5 to 10 days
Acute community-acquired pneumonia	400 mg	200 mg Q 12 hours	14 days
Acute bacterial exacerbations of chronic bronchitis	400 mg	200 mg Q 12 hours	10 days
Uncomplicated gonorrhea (men and women) and rectal gonococcal infections (women)	200 mg	single dose
Skin and skin structure	800 mg	400 mg Q 12 hours	7 to 14 days
Acute maxillary sinusitis	400 mg	200 mg Q 12 hours	10 days
Uncomplicated urinary tract infection	200 mg	100 mg Q 12 hours	7 days

Cefpodoxime proxetil oral suspension may be given without regard to food. The recommended dosages, durations of treatment, and applicable patient populations are as described in the following chart:

Adults and Adolescents (age 12 years and older):

Type of Infection	Total Daily Dose	Dose Frequency	Duration
Pharyngitis and/or tonsillitis	200 mg	100 mg Q 12 hours	5 to 10 days
Acute community-acquired pneumonia	400 mg	200 mg Q 12 hours	14 days
Uncomplicated gonorrhea (men and women) and rectal gonococcal infections (women)	200 mg	single dose
Skin and skin structure	800 mg	400 mg Q 12 hours	7 to 14 days
Acute maxillary sinusitis	400 mg	200 mg Q 12 hours	10 days
Uncomplicated urinary tract infection	200 mg	100 mg Q 12 hours	7 days

Infants and Pediatric Patients (age 2 months through 12 years):

Type of Infection	Total Daily Dose	Dose Frequency	Duration
Acute otitis media	10 mg/kg/day (Max 400 mg/day)	5 mg/kg Q 12 h (Max 200 mg/dose)	5 days
Pharyngitis and/or tonsillitis	10 mg/kg/day (Max 200 mg/day)	5 mg/kg/dose Q 12 h (Max 100 mg/dose)	5 to 10 days
Acute maxillary sinusitis	10 mg/kg/day (Max 400 mg/day)	5 mg/kg Q 12 hours (Max 200 mg/dose)	10 days

For patients with severe renal impairment (<30 mL/min creatinine clearance), the dosing intervals should be increased to Q 24 hours. In patients maintained on hemodialysis, the dose frequency should be 3 times/week after hemodialysis.



When only the serum creatinine level is available, the following formula (based on sex, weight, and age of the patient) may be used to estimate creatinine clearance (mL/min). For this estimate to be valid, the serum creatinine level should represent a steady state of renal function.



Males:                                     

(mL/min)                                 72 x serum creatinine (mg/100 mL)



Females:                                  0.85 x above value

(mL/min)



Cefpodoxime pharmacokinetics in cirrhotic patients (with or without ascites) are similar to those in healthy subjects. Dose adjustment is not necessary in this population.

In clinical trials using of cefpodoxime proxetil film-coated tablets, 4696 patients were treated with the recommended dosages of cefpodoxime (100 to 400 mg Q 12 hours). There were no deaths or permanent disabilities thought related to drug toxicity. One-hundred twenty-nine (2.7%) patients discontinued medication due to adverse events thought possibly or probably related to drug toxicity. Ninety-three (52%) of the 178 patients who discontinued therapy (whether thought related to drug therapy or not) did so because of gastrointestinal disturbances, nausea, vomiting, or diarrhea. The percentage of cefpodoxime proxetil-treated patients who discontinued study drug because of adverse events was significantly greater at a dose of 800 mg daily than at a dose of 400 mg daily or at a dose of 200 mg daily. Adverse events thought possibly or probably related to cefpodoxime in multiple-dose clinical trials (N=4696 cefpodoxime-treated patients) were:







Diarrhea                                  7%



Diarrhea or loose stools were dose-related: decreasing from 10.4% of patients receiving 800 mg per day to 5.7% for those receiving 200 mg per day. Of patients with diarrhea, 10% had organism or toxin in the stool. (See .)



Nausea                                    3.3%

Vaginal Fungal Infections     1%

Vulvovaginal Infections        1.3%

Abdominal Pain                     1.2%

Headache                               1%















  - fungal infections, abdominal distention, malaise, fatigue, asthenia, fever, chest pain, back pain, chills, generalized pain, abnormal microbiological tests, moniliasis, abscess, allergic reaction, facial edema, bacterial infections, parasitic infections, localized edema, localized pain.



  - congestive heart failure, migraine, palpitations, vasodilation, hematoma, hypertension, hypotension.



  - vomiting, dyspepsia, dry mouth, flatulence, decreased appetite, constipation, oral moniliasis, anorexia, eructation, gastritis, mouth ulcers, gastrointestinal disorders, rectal disorders, tongue disorders, tooth disorders, increased thirst, oral lesions, tenesmus, dry throat, toothache.



  - anemia.



  - dehydration, gout, peripheral edema, weight increase.



  - myalgia.



  - dizziness, insomnia, somnolence, anxiety, shakiness, nervousness, cerebral infarction, change in dreams, impaired concentration, confusion, nightmares, paresthesia, vertigo.



- asthma, cough, epistaxis, rhinitis, wheezing, bronchitis, dyspnea, pleural effusion, pneumonia, sinusitis.



- urticaria, rash, pruritus non-application site, diaphoresis, maculopapular rash, fungal dermatitis, desquamation, dry skin non-application site, hair loss, vesiculobullous rash, sunburn. 



  - taste alterations, eye irritation, taste loss, tinnitus. 



  - hematuria, urinary tract infections, metrorrhagia, dysuria, urinary frequency, nocturia, penile infection, proteinuria, vaginal pain. 



 



In clinical trials using multiple doses of cefpodoxime proxetil granules for oral suspension, 2128 pediatric patients (93% of whom were less than 12 years of age) were treated with the recommended dosages of cefpodoxime (10 mg/kg/day Q 24 hours or divided Q 12 hours to a maximum equivalent adult dose). There were no deaths or permanent disabilities in any of the patients in these studies. Twenty-four patients (1.1%) discontinued medication due to adverse events thought possibly or probably related to study drug. Primarily, these discontinuations were for gastrointestinal disturbances, usually diarrhea, vomiting, or rashes. 



Adverse events thought possibly or probably related, or of unknown relationship to cefpodoxime proxetil for oral suspension in multiple-dose clinical trials (N=2128 patients treated with cefpodoxime) were: 



:



Diarrhea                                              6% 



The incidence of diarrhea in infants and toddlers (age 1 month to 2 years) was 12.8%. 



Diaper rash/Fungal skin rash               2% (includes moniliasis)



The incidence of diaper rash in infants and toddlers was 8.5%. 



Other skin rashes                                 1.8%

Vomiting                                              2.3%



:



Localized abdominal pain, abdominal cramp, headache, monilia, generalized abdominal pain, asthenia, fever, fungal infection.



Nausea, monilia, anorexia, dry mouth, stomatitis, pseudomembranous colitis.



Thrombocythemia, positive direct Coombs’ test, eosinophilia, leukocytosis, leukopenia, prolonged partial thromboplastin time, thrombocytopenic purpura.



Increased SGPT.



Myalgia.



Hallucination, hyperkinesia, nervousness, somnolence.



Epistaxis, rhinitis.



Skin moniliasis, urticaria, fungal dermatitis, acne, exfoliative dermatitis, maculopapular rash.



Taste perversion.



:



In clinical trials using of cefpodoxime proxetil film-coated tablets, 509 patients were treated with the recommended dosage of cefpodoxime (200 mg). There were no deaths or permanent disabilities thought related to drug toxicity in these studies.



Adverse events thought possibly or probably related to cefpodoxime in single-dose clinical trials conducted in the United States were: 



:



Nausea                                                1.4%

Diarrhea                                              1.2%



:



: Dizziness, headache, syncope. : Rash.

: Vaginitis.

: Abdominal pain.

: Anxiety.







Significant laboratory changes that have been reported in adult and pediatric patients in clinical trials of cefpodoxime proxetil, without regard to drug relationship, were: 



Transient increases in AST (SGOT), ALT (SGPT), GGT, alkaline phosphatase, bilirubin, and LDH. 



Eosinophilia, leukocytosis, lymphocytosis, granulocytosis, basophilia, monocytosis, thrombocytosis, decreased hemoglobin, decreased hematocrit, leukopenia, neutropenia, lymphocytopenia, thrombocytopenia, thrombocythemia, positive Coombs’ test, and prolonged PT, and PTT. 



Hyperglycemia, hypoglycemia, hypoalbuminemia, hypoproteinemia, hyperkalemia, and hyponatremia. 



Increases in BUN and creatinine. 



Most of these abnormalities were transient and not clinically significant. 







The following serious adverse experiences have been reported: allergic reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme and serum sickness-like reactions, pseudomembranous colitis, bloody diarrhea with abdominal pain, ulcerative colitis, rectorrhagia with hypotension, anaphylactic shock, acute liver injury, exposure with miscarriage, purpuric nephritis, pulmonary infiltrate with eosinophilia, and eyelid dermatitis. 



One death was attributed to pseudomembranous colitis and disseminated intravascular coagulation. 







In addition to the adverse reactions listed above which have been observed in patients treated with cefpodoxime proxetil, the following adverse reactions and altered laboratory tests have been reported for cephalosporin class antibiotics: 



Renal dysfunction, toxic nephropathy, hepatic dysfunction including cholestasis, aplastic anemia, hemolytic anemia, serum sickness-like reaction, hemorrhage, agranulocytosis, and pancytopenia.



Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced. (See and ) If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.

Concomitant administration of high doses of antacids (sodium bicarbonate and aluminum hydroxide) or H₂ blockers reduces peak plasma levels by 24% to 42% and the extent of absorption by 27% to 32%, respectively. The rate of absorption is not altered by these concomitant medications. Oral anti-cholinergics (e.g., propantheline) delay peak plasma levels (47% increase in T_max), but do not affect the extent of absorption (AUC). As with other beta-lactam antibiotics, renal excretion of cefpodoxime was inhibited by probenecid and resulted in an approximately 31% increase in AUC and 20% increase in peak cefpodoxime plasma levels.

Although nephrotoxicity has not been noted when cefpodoxime proxetil was given alone, close monitoring of renal function is advised when cefpodoxime proxetil is administered concomitantly with compounds of known nephrotoxic potential.